The long range goal of the project is to identify and understand the control and volue of the various fetoplacental adaptations to repetitive, progressive pancental damage using a longitudinal correlative approach. The health related implications lie in improving our understanding of the pathophysiology of uteroplacental insufficinecy and intrauterine growth retardation. The first specific goal is to assess the impact of a disruption in homeostasis on fetal well-being and central nervous system damage in growth retardation as evaluation by functional (hemodynamic, metabolic, electroencephalographic) and neuropathologic criteria. We will examine the uteroplacental and fetal response to both changes in matermal blood volume and to an increased carbohydrate substrate load. In these experiments, multiple maternal, uterine and fetal parameters will be monitored before, during and after a change in environmental conditions and correlated with on another and with brain function and structure. The second specific goal is to continue to explore the mechanisms utilized by the fetus in successfully adapting to progressive placental compromise. This will be examined by assessing changes in: fetoplacental blood volume; placental perfusion balance; the distribution of blood blow within the fetal cerebral circulation; and, the relationship between multiple parameters and the fetoplacental endocrine (cortisol, prolactin, progesterone) profile, in response to repetitive embolization of the uterine vasculature. In these experiments logitudinal measurements of hemodynamic, metabolic, electroencephalographic, and endocrine parameters will be followed by distributional flow studies at term in control and embolized animals. We will continue to utilize our chronically instrumented pregnant ewe preparation with placental vascular insufficiency. Specific technical methodology will include: 1) flow transducer and microsphere measurement of total flow and it distribution; 2) direct recording of electrocortical potentials and cordiovascular parameters; 3) gross and microscopic examination of brain structure; 4) specific hormaonal radioimmunoassay; and, 5) conventional methodology for pH, p02, pCO2, oxygen, glucose, amino acid, lactate and pyruvate content.